1. Field of the Invention
The present invention is directed to a novel process for preparing omega-halo-ketones such as 6-chloro-2-hexanone.
6-Chloro-2-hexanone is a final intermediate in the manufacture of the vasodilator drug pentoxifylline, commonly sold under the trademark Trental. The current manufacturing process for 6-chloro-2-hexanone is a three-step process starting from ethyl acetoacetate such as that described in Organic Synthesis, Collective Volume 5, Gilman, H. Ed.; John Wiley, N.Y. (1932), pages 248-251 and 350-353. Atom efficiency of this process is modest (37%), since a molecule, each of ethanol and carbon dioxide, are lost per molecule of product made. Sodium bromide is formed as a by-product, making waste disposal an issue as well. Consequently, it is desirable to overcome these deficiencies and provide a more efficient, low- cost method to produce 6-chloro-2-hexanone.
2. Description of the Prior Art
The following prior art references are disclosed in accordance with the terms of 37 CFR 1.56, 1.93, and 1.97.
U.S. Pat. No. 2,497,349 discloses a process for preparing alicyclic alcohols from various hydrocarbons including methylcyclopentane.
U.S. Pat. No. 2,615,921 discloses a process for the oxidation of naphthenic hydrocarbons including methylcyclopentane.
U.S. Pat. No. 2,675,402 discloses a process for preparing tertiary cycloaliphatic hypohalites such as methylcyclopentyl hypochlorite.
U.S. Pat. No. 2,691,682 discloses a process for preparing omega-halo-ketones by rearrangement of tertiary cycloaliphatic hypohalites including the preparation of 6-chlorohexan-2-one by rearrangement of 1-methylcyclopentyl hypochlorite.
U.S. Pat. No. 3,391,190 discloses a continuous process for oxidizing lower alkanes and cycloalkanes, particularly cyclohexane, to ketones and alcohols.
U.S. Pat. No. 3,737,433 discloses certain oxoalkyldimethyl-xanthines for use in the pharmaceutical area.
U.S. Pat. No. 4,189,469 discloses pharmaceutical compositions for oral administration containing xanthine derivatives.
U.S. Pat. No. 4,260,845 discloses a zinc aluminate dehydration catalyst, suitably activated, as by heating in air, which is employed to dehydrate a saturated alcohol (such as cyclohexanol) to produce an olefin.
U.S. Pat. No. 4,588,846 discloses a process for producing a cyclic alcohol (such as cyclopentanol) by catalytic hydration of a cyclic olefin (such as cyclopentene) in a liquid phase.
U.S. Pat. No. 4,661,639 discloses a process for producing a cyclic alcohol (such as cyclohexanol) by catalytic hydration of a cyclic olefin (such as cyclohexene).
U.S. Pat. No. 4,849,550 discloses a method for producing cycloalkanols by the hydration of cycloalkenes (such as methylcyclopentane) with aromatic sulfonic acids as a catalyst.
Journal of the American Chemical Society, December 1948, pp. 4041-4045 discloses the isomerization of cyclohexenes to cyclopentenes.
All of the above cited prior art and any other references mentioned herein are incorporated herein by reference in their entirety.